THU0532 Estrogen Upregulates Interleukin-21 Production of Clusters of Differentiation 4 Positive T Lymphocytes in Patients with Systemic Lupus Erythematosus. (10th June 2014)

• Record Type: Journal Article
• Authors: Lee, J.; Koh, J.H.; Min, H.K.; Kang, J.Y.; Suh, Y.S.; Lee, J.-H.; Jung, S.-M.; Lee, J.Y.; Kim, J.-M.; Kwok, S.-K.; Ju, J.H.; Park, K.-S.; Kim, H.-Y.; Park, S.-H.
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Supplement 2(2014)
• Page Start: 367
• Page End: 367
• Publication Date: 2014-06-10
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-eular.3160
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Systemic lupus erythematosus (SLE) is an autoimmune disease in which various organs and tissues are damaged through abnormal immune responses mediated by tissue-binding autoantibodies and immune complex deposition. As the majority of SLE patients are women of child-bearing age, estrogen has been suggested to play an important role in the pathogenesis of SLE. One of the proposed roles of estrogen is to increase autoantibody production. IL-21, a common-γ chain cytokine, has been shown to be crucial in the differentiation of activated B cells into plasma cells. Objectives: Based on these concepts, we investigated the effect of estrogen on the production of IL-21 by T cells and subsequent B cell activation in SLE patients. Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from peripheral blood of 23 SLE patients and 16 healthy controls. CD4+ T cells, non CD4+ T cells and B cells were isolated using microbeads. Isolated cells were treated with 17-β estradiol at various concentrations for 48hrs. The expression of IL-21 and its receptor was assessed by measuring the level of protein and mRNA using ELISA and RT-PCR, respectively. The level of immunoglobulin G was measured with specific ELISA. Results: The expression of IL-21 and its receptor in serum, PBMCs, and CD4+ T cells were higher in the patients with SLE compared to healthy controls. Exposure of CD4+ T cells from SLE patients to 17-β estradiol leads to a dose-and time-dependent increase in the IL-21 expression. The increase was abolished in the presence of MAP kinase (MEK, p38, JNK) inhibitors. B cells of healthy controls showed an increased antibody production when they were co-cultured with estrogen treated CD4+ T cells of patients with SLE. Treatment with anti-IL-21 antibody abrogated the increased antibody production of the co-culture systems, suggesting the increase was mediated by IL-21 dependent manner. Conclusions: Estrogen upregulates IL-21 expression of CD4+ T cells via MAPK dependent pathways in SLE patients, which in turn induces increased antibody production by B cells. Disclosure of Interest: : None declared DOI: 10.1136/annrheumdis-2014-eular.3160